Obeticholic acid as a tablet is in clinical development for the treatment of advanced liver fibrosis due to non-alcoholic steatohepatitis (NASH). Non-alcoholic fatty liver disease (NAFLD) is the general term for conditions in which an excessive amount of fat is stored in the liver, but where this excess is not caused by heavy alcohol use. A build-up of fat alone is called simple fatty liver (steatosis). NASH occurs when the presence of fat leads to liver cell damage and inflammation (hepatitis). Over time, liver cell damage and inflammation due to NASH can cause scarring (fibrosis) of the liver which may increase until advanced. Once there is advanced fibrosis due to NASH, there is a higher risk of progression to cirrhosis and its complications such as liver failure, liver cancer, and death. Although simple fatty liver, NASH, and advanced fibrosis due to NASH are distinct types of NAFLD in terms of the risk to health they pose, they are considered stages of the same disease through which people will progress if lifestyle interventions are not effective.
Obeticholic acid is a modified form of a bile acid. It works by attaching to receptors in the liver and gut called farnesoid X receptors (FXRs) which control the production of bile. By attaching to these receptors, obeticholic acid reduces the production of bile in the liver, preventing it from building up and damaging the liver tissue. FXRs are also involved in the control of inflammation and fibrosis as well as the handling of fats and glucose in the liver which are important processes in the development of NASH. If licensed, obeticholic acid may offer the first pharmacological treatment option for patients with NASH who currently have few effective therapies available.
Etrolizumab is a new monoclonal antibody (an immune protein) delivered by subcutaneous injection. The treatment works by targeting molecules called integrins to control the immune response and prevent the accumulation of immune molecules, which cause inflammation in individuals with a form of ulcerative colitis where inflammation is not mediated by a signalling protein called tumour necrosis factors (TNF) alpha (‘non-TNF-α’) and who are therefore intolerant to TNF blockers. This represents a new target group as current therapies focus mainly on anti-TNF inflammation. In one study, etrolizumab showed a greater reduction of intestinal lymphocyte infiltration in comparison to standard treatment.